tbuckley/cabot-search huggingface dataset:
Mutations in the alternative complement pathway in multiple myeloma patients with carfilzomib-induced thrombotic microangiopathy
Authors: Maria Moscvin, Christine Ivy Liacos, Tianzeng Chen, Foteini Theodorakakou, Despina Fotiou, Shahrier Hossain, Sean Rowell, Houry Leblebjian, Eileen Regan, Peter Czarnecki, Filippo Bagnoli, Niccolo’ Bolli, Paul Richardson, Helmut G. Rennke, Meletios A. Dimopoulos, Efstathios Kastritis, Giada Bianchi
Journal: Blood Cancer Journal (2023)

Thrombotic microangiopathy (TMA) has been reported to occur in multiple myeloma (MM) patients in association with treatment with carfilzomib, an irreversible proteasome inhibitor (PI). The hallmark of TMA is vascular endothelial damage leading to microangiopathic hemolytic anemia, platelet consumption, fibrin deposition and small-vessel thrombosis with resultant tissue ischemia. The molecular mechanisms underlying carfilzomib-associated TMA are not known. Germline mutations in the complement alternative pathway have been recently shown to portend increased risk for the development of atypical hemolytic uremic syndrome (aHUS) and TMA in the setting of allogeneic stem cell transplant in pediatric patients. We hypothesized that germline mutations in the complement alternative pathway may similarly predispose MM patients to carfilzomib-associated TMA. We identified 10 MM patients with a clinical diagnosis of TMA in the context of carfilzomib treatment and assessed for the presence of germline mutations in the complement alternative pathway. Ten, matched MM patients exposed to carfilzomib but without clinical TMA were used as negative controls. We identified a frequency of deletions in the complement Factor H genes 3 and 1 (delCFHR3-CFHR1) and genes 1 and 4 (delCFHR1-CFHR4) in MM patients with carfilzomib-associated TMA that was higher as compared to the general population and matched controls. Our data suggest that complement alternative pathway dysregulation may confer susceptibility to vascular endothelial injury in MM patients and predispose to development of carfilzomib-associated TMA. Larger, retrospective studies are needed to evaluate whether screening for complement mutations may be indicated to properly counsel patients about TMA risk with carfilzomib use.
Electrocardiographic Predictors of Cardiovascular Outcome in Women
Authors: Brian Triola, Marian B. Olson, Steven E. Reis, Pentti Rautaharju, C. Noel Bairey Merz, Sheryl F. Kelsey, Leslee J. Shaw, Barry L. Sharaf, George Sopko, Samir Saba
Journal: Journal of the American College of Cardiology (2005)
Life-Threatening Hemoptysis in Mitral Stenosis
Authors: Morton A. Diamond
Journal: JAMA (1971)

A 32-year-old patient with mitral stenosis and a long history of recurrent hemoptysis was hospitalized because of life-threatening pulmonary bleeding, and required transfusion of 34 units of whole blood. Emergency insertion of a Starr-Edwards ball valve prosthesis resulted in prompt cessation of hemorrhage, and at nine months follow-up, the hemorrhage has not recurred. Review of 14 cases of patients with massive hemoptysis associated with mitral stenosis (seven operated upon and seven not operated upon) reveals that five of the conservatively treated patients died, in contrast to only two who died in the group operated upon. Mitral valve surgery appears to be consistently associated with rapid and sustained cessation of hemoptysis. Therefore, surgery should be considered in hemoptysis due to mitral stenosis, particularly when the danger of asphyxiation exists.
Collagen synthesis by human liver (myo)fibroblasts in culture: evidence fora regulatory role of IL-1β,IL-4, TGFβ and IFN gamma
Authors: Anke M.B.C. Tiggelman, Willem Boers, Christiaan Linthorst, Mieke Sala, Robert A.E.M. Chamuleau
Journal: Journal of Hepatology (1995)
Neoplasms in Children Treated With X Rays for Thymic Enlargement. II. Tumor Incidence as a Function of Radiation Factors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Edward T. Toyooka, James W. Pifer, S. Lee Crump, Arthur M. Dutton, Louis H. Hempelmann
Journal: JNCI Journal of the National Cancer Institute (1963)

The tumor incidence in 2,809 children treated with X rays for thymic enlargement was analyzed in terms of the dose and other radiation factors. Because of the small number of specific types of neoplasms, the tumors were combined for analysis into three categories: 1) all thyroid tumors, 2) other tumors inside the directly treated tissues, and 3) tumors outside the directly treated tissues. A striking increase of all neoplasms, less marked for tumors outside the treated tissues, was noted as the children grew older. This complicated the analysis because the older children usually received higher doses through larger ports, frequently placed posteriorly as well as anteriorly. When the age relationship was corrected by the use of cohort-analysis, a given air dose administered half anteriorly and half posteriorly to the chest was associated with a significantly higher tumor incidence than that observed when the same total dose was given only anteriorly. The incidence of thyroid tumors was considerably higher with the former technique. Irradiation both anteriorly and posteriorly was also associated with a strong tendency of the tumors to cluster in primary irradiated tissues, a phenomenon not as pronounced when anterior irradiation alone was used. Attempts to demonstrate a dose dependence for the major treatment groups, i.e., combined anterior and posterior, and anterior treatments were unsuccessful. The failure to show a dose response was attributed to the small number of neoplasms, rather than to definite evidence of an absence of such an effect. The clustering of tumors in the directly irradiated tissues and the apparent effect of port arrangement on tumor incidence constitute strong circumstantial evidence favoring radiation exposure as an etiologic factor in tumor production. The apparent effectiveness of combined anterior and posterior irradiation in inducing tumors could be due to exposure of certain tissues in the head and neck with this port arrangement. These tissues, including the pituitary gland, were not likely to be exposed when anterior ports alone were used. Possibly the 2-week interval between treatments of the group of children with the highest tumor incidence also augmented the oncogenic action of the radiation exposure.
Cancer Incidence in a Cohort of Patients With Seizure Disorders&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Sally B. Shirts, John F. Annegers
 4, W. Allen Hauser, Leonard T. Kurland
Journal: JNCI Journal of the National Cancer Institute (1986)

The incidence of cancer was evaluated in a population- based cohort of 959 patients diagnosed with seizure disorders while residents of Rochester, MN, between 1935 and 1979. For all cancer sites combined, there were 65 incidence cases for a standard morbidity ratio of 1.4. Most of the excess was attributable to a 22-fold increase in the incidence of primary brain tumors among these patients. Most of the brain tumors occurred within 5 years of the seizure disorder diagnosis, suggesting that the seizure disorder was due to the brain tumor. The incidence of cancer of other sites, exclusive of brain, was not elevated. There was no evidence of an association of cancer incidence with duration of seizures or with the use of anticonvulsant drugs.
Expression and Hypomethylation of α-Fetoprotein Gene in Unicentric and Multicentric Human Hepatocellular Carcinomas
Authors: Shian-Yang Peng, Hey-Chi Hsu, Po-Lin Lai, Po-Tah Tsung, Juan-Shiu Chu, Po-Huang Lee, Ding-Shin Chen
Journal: Hepatology (1993)

The messenger RNA and DNA methylation of the α-fetoprotein gene were studied in 101 resected primary hepatocellular carcinomas, of which 93 were unicentric and 8 were multicentric. Fifty-five were 5 cm or less in diameter (small) and 46 were more than 5 cm in diameter (large). In 48.5% of the cases, we detected α-fetoprotein messenger RNA in hepatocellular carcinomas, more frequently in large (60.9%) than in small (38.2%; p &lt; 0.00001) but not in any of the nontumorous livers. The α-fetoprotein messenger RNA was detected in 83%, 70% and 6.8% of patients with serum α-fetoprotein levels of 320 ng/ml or more, 100 to 319 ng/ml and less than 100 ng/ml, respectively. This finding suggests that α-fetoprotein gene expression in hepatocellular carcinoma contributes to the serum α-fetoprotein elevation in patients with hepatocellular carcinoma. α-Fetoprotein messenger RNA appeared as a major band of 2.4 kb, with two minor species of about 6.5 and 3.6 kb in the hepatocellular carcinoma and the fetal liver. Hypomethylation of the 5′ end of the α-fetoprotein gene was detected in 78.3% of hepatocellular carcinomas expressing α-fetoprotein messenger RNA but infrequently (16.7%) in hepatocellular carcinomas with no detectable α-fetoprotein messenger RNA (p &lt; 0.0003). This finding suggests that hypomethylation at the 5′ region of the gene is associated with α-fetoprotein gene reexpression in hepatocellular carcinoma. The α-fetoprotein gene expression helped to differentiate unicentric from multicentric hepatocellular carcinomas and to identify other hidden α-fetoprotein-secreting hepatocellular carcinomas. The α-fetoprotein gene expression occurred more often in patients younger than 30 yr old (100% vs. 41.2%; p &lt; 0.002), in HBsAg-seropositive patients (53.2% vs. 33.3%; p &lt; 0.03) and in patients with poorly differentiated hepatocellular carcinoma (56% vs. 23.1%; p &lt; 0.003). Patients with unicentric small hepatocellular carcinomas expressing α-fetoprotein messenger RNA or serum α-fetoprotein elevation had a worse 2-yr survival rate than those with neither α-fetoprotein messenger RNA expression nor serum α-fetoprotein elevation (70.6% vs. 94.7%; p &lt; 0.02). We conclude that the α-fetoprotein gene expression in hepatocellular carcinoma possesses biological significance. (Hepatology 1993;17:35-41.)
Colorectal cancers with microsatellite instability display mRNA expression signatures characteristic of increased immunogenicity
Authors: Ayan Banerjea, Shafi Ahmed, Rebecca E Hands, Fei Huang, Xia Han, Peter M Shaw, Roger Feakins, Stephen A Bustin, Sina Dorudi
Journal: Molecular Cancer (2004)

Colorectal cancers displaying high-degree microsatellite instability (MSI-H) have an improved prognosis compared to microsatellite stable (MSS) cancers. The observation of pronounced lymphocytic infiltrates suggests that MSI-H cancers are inherently more immunogenic. We aimed to compare the gene expression profiles of MSI-H and MSS cancers to provide evidence for an activated immune response in the former. We analysed tissue from 133 colorectal cancer patients with full consent and Local Ethics Committee approval. Genomic DNA was analysed for microsatellite instability in BAT-26. High-quality RNA was used for microarray analysis on the Affymetrix® HG-U133A chip. Data was analysed on GeneSpring software version 6.0. Confirmatory real-time RT-PCR was performed on 28 MSI-H and 26 MSS cancers. A comparison of 29 MSI-H and 104 MSS cancers identified 2070 genes that were differentially expressed between the two groups [P < 0.005]. Significantly, many key immunomodulatory genes were up-regulated in MSI-H cancers. These included antigen chaperone molecules (HSP-70, HSP-110, Calreticulin, gp96), pro-inflammatory cytokines (Interleukin (IL)-18, IL-15, IL-8, IL-24, IL-7) and cytotoxic mediators (Granulysin, Granzyme A). Quantitative RT-PCR confirmed up-regulation of HSP-70 [P = 0.016], HSP-110 [P = 0.002], IL-18 [P = 0.004], IL-8 [0.002] and Granulysin [P < 0.0001]. The upregulation of a large number of genes implicated in immune response supports the theory that MSI-H cancers are immunogenic. The novel observation of Heat Shock Protein up-regulation in MSI-H cancer is highly significant in light of the recognised roles of these proteins in innate and antigen-specific immunogenicity. Increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators also indicate an activated anti-tumour immune response.
Missense Mutations in the Fas Gene Resulting in Autoimmune Lymphoproliferative Syndrome: A Molecular and Immunological Analysis
Authors: Alessandra Bettinardi, Duilio Brugnoni, Eugenia Quiròs-Roldan, Alberto Malagoli, Stefania La Grutta, Antonio Correra, Luigi D. Notarangelo
Journal: Blood (1997)
Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock
Authors: Edward Abraham, Antonio Anzueto, Guillermo Gutierrez, Sidney Tessler, Gerry San Pedro, Richard Wunderink, Anthony Dal Nogare, Stanley Nasraway, Steve Berman, Robert Cooney, Howard Levy, Robert Baughman, Mark Rumbak, R Bruce Light, Lona Poole, Randy Allred, John Constant, James Pennington, Steven Porter
Journal: The Lancet (1998)
Progress Toward In Vivo Use of siRNAs-II
Authors: Garrett R Rettig, Mark A Behlke
Journal: Molecular Therapy (2011)

RNA interference (RNAi) has been extensively employed for in vivo research since its use was first demonstrated in mammalian cells 10 years ago. Design rules have improved, and it is now routinely possible to obtain reagents that suppress expression of any gene desired. At the same time, increased understanding of the molecular basis of unwanted side effects has led to the development of chemical modification strategies that mitigate these concerns. Delivery remains the single greatest hurdle to widespread adoption of in vivo RNAi methods. However, exciting advances have been made and new delivery systems under development may help to overcome these barriers. This review discusses advances in RNAi biochemistry and biology that impact in vivo use and provides an overview of select publications that demonstrate interesting applications of these principles. Emphasis is placed on work with synthetic, small interfering RNAs (siRNAs) published since the first installment of this review which appeared in 2006. RNA interference (RNAi) has been extensively employed for in vivo research since its use was first demonstrated in mammalian cells 10 years ago. Design rules have improved, and it is now routinely possible to obtain reagents that suppress expression of any gene desired. At the same time, increased understanding of the molecular basis of unwanted side effects has led to the development of chemical modification strategies that mitigate these concerns. Delivery remains the single greatest hurdle to widespread adoption of in vivo RNAi methods. However, exciting advances have been made and new delivery systems under development may help to overcome these barriers. This review discusses advances in RNAi biochemistry and biology that impact in vivo use and provides an overview of select publications that demonstrate interesting applications of these principles. Emphasis is placed on work with synthetic, small interfering RNAs (siRNAs) published since the first installment of this review which appeared in 2006.
Prevalence and Correlates of Herpes Simplex Infections
Authors: David Siegel
Journal: JAMA (1992)

<h3>Objective.</h3> —To examine the extent and correlates of infection with herpes Simplex virus type 1 (HSV-1) and type 2 (HSV-2) in an inner-city community, we studied the prevalence of antibodies to these viruses and their association with risk behaviors in a representative sample of unmarried white, black, and Hispanic adults living in San Francisco, Calif. <h3>Design.</h3> —Cross-sectional, community-based, random household survey. <h3>Participants.</h3> —In 1988 and 1989, we surveyed 1770 unmarried men and women aged 20 to 44 years from three San Francisco neighborhoods of varying geographic and cultural characteristics. <h3>Main Outcome Measures.</h3> —HSV-1 and HSV-2 antibodies based on an immunodot assay using type-specific glycoproteins gG-1 and gG-2. <h3>Results.</h3> —Of blood samples from 1212 participants available for testing, 750 (62%) had HSV-1 antibodies and 400 (33%) had HSV-2 antibodies. After controlling for other variables, HSV-1 antibody was significantly correlated (<i>P</i>&lt;.05) with older age (in heterosexual men, women, and homosexually active men), less education (in heterosexual men and women), and Hispanic (especially those not born in the United States) or black race. HSV-2 antibody was significantly correlated (<i>P</i>&lt;.05) with female gender, number of lifetime sexual partners and older age (in heterosexual men and women), and low levels of education and black or Hispanic race (in women). Among those with antibody to HSV-2, only 28(19%) of 149 men and 32 (13%) of 251 women reported a history of genital herpes. However, most men (62%) and women (84%) who reported a history of genital herpes had HSV-2 antibodies. We observed a similar pattern (low sensitivity and moderate specificity) for a history of facial herpes and the presence of HSV-1 antibodies. After controlling for other variables, HSV-2 antibodies were associated with a lower frequency of HSV-1 antibodies among homosexual men infected with the human immunodeficiency virus. <h3>Conclusions.</h3> —HSV-1 antibodies were found in nearly two thirds of single urban adults and were most common among Hispanics not born in the United States. HSV-2 antibodies were found in one third of this population and were associated with risk behaviors for sexually transmitted diseases. For both facial and genital herpes infections, self-reporting of infection was very insensitive and moderately specific. (<i>JAMA</i>. 1992;268:1702-1708)
High prevalence of hepatitis C virus infection in patients with B‐cell lymphoproliferative disorders in Italy
Authors: Gennaro De Rosa, Maria Luisa Gobbo, Amalia De Renzo, Rosario Notaro, Salvatore Garofalo, Maria Grimaldi, Aurora Apuzzo, Federico Chiurazzi, Marco Picardi, Margherita Matarazzo, Bruno Rotoli
Journal: American Journal of Hematology (1997)
Role of Foods in Sporadic Listeriosis
Authors: Anne Schuchat
Journal: JAMA (1992)

<h3>Objective.</h3> —To identify dietary risk factors for sporadic listeriosis. <h3>Design.</h3> —Case-control study with blinded telephone interviews. <h3>Setting.</h3> —Multistate population of 18 million persons, November 1988 through December 1990. <h3>Participants.</h3> —One hundred sixty-five patients with culture-confirmed listeriosis and 376 control subjects matched for age, health care provider, and immunosuppressive condition. <h3>Results.</h3> —The annual incidence of invasive listeriosis was 7.4 cases per million population; 23% of the infections were fatal. Cases were more likely than matched controls to have eaten soft cheeses (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.4 to 4.8;<i>P</i>=.002) or food purchased from store delicatessen counters (OR, 1.6; 95% CI, 1.0 to 2.5;<i>P</i>=.04); 32% of sporadic disease could be attributed to eating these foods. Sixty-nine percent of cases in men and nonpregnant women occurred in cancer patients, persons with the acquired immunodeficiency syndrome, organ transplant recipients, or those receiving corticosteroid therapy. Among these immunosuppressed patients, eating undercooked chicken also increased the risk of listeriosis (OR, 3.3; 95% CI, 1.2 to 9.2;<i>P</i>=.02 <h3>Conclusions.</h3> —Foodborne transmission may account for a substantial portion of sporadic listeriosis. Prevention efforts should include dietary counseling of high-risk patients and continued monitoring of food production. (<i>JAMA</i>. 1992;267:2041-2045)
Human CD34+ Cells Express CXCR4 and Its Ligand Stromal Cell–Derived Factor-1. Implications for Infection by T-Cell Tropic Human Immunodeficiency Virus
Authors: Alessandro Aiuti, Lucia Turchetto, Manuela Cota, Arcadi Cipponi, Andrea Brambilla, Cinzia Arcelloni, Rita Paroni, Elisa Vicenzi, Claudio Bordignon, Guido Poli
Journal: Blood (1999)
Long-term clinical and histopathological follow-up of chronic posttransfusion hepatitis
Authors: Adrian M. di Bisceglie, Zachary D. Goodman, Kamal G. Ishak, Jay H. Hoofnagle, Jacqueline J. Melpolder, Harvey J. Alter
Journal: Hepatology (1991)

We have evaluated the clinical and histopathological outcomes of patients who contracted chronic non A, non B hepatitis as a result of transfusions administered during heart surgery at the National Institutes of Health. Posttransfusion hepatitis developed in 65 of 1,070 (6.1%) patients and became chronic in 45 (69%) of those cases. Antibody to hepatitis C virus was detectable in 53 patients (82%) with posttransfusion non A, non B hepatitis. Thirty-three patients with chronic non A, non B hepatitis agreed to liver biopsy (group 1). In addition, six other patients with chronic posttransfusion non A, non B hepatitis were evaluated (group 2). These 39 patients were followed between 1 and 24 yr (mean = 9.7 yr). Cirrhosis developed in 8 patients (20%) between 1.5 and 16 yr after blood transfusion. Of the 33 patients in group 1, 11 (33%) died during follow-up. In two cases (6%), this was related to liver failure. At this writing, two additional patients (6%) have decompensated cirrhosis and one (3%) has debilitating fatigue. Twenty of 33 patients (61%) with histological evidence of chronic active hepatitis or cirrhosis are asymptomatic and have no clinical evidence of liver disease. Thus chronic non A, non B posttransfusion hepatitis appeared to be due to hepatitis C virus infection in most cases. It was associated with the development of cirrhosis in approximately 20% of cases and end-stage liver disease in 12% of patients followed prospectively. Most patients with histological evidence of cirrhosis or chronic active hepatitis, however, had minimal clinical evidence of liver disease within the time frame of this study. (Hepatology 1991;14:969-974.)